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Open Access Research article

Autoantibodies against MHC class I polypeptide-related sequence A are associated with increased risk of concomitant autoimmune diseases in celiac patients

Antonio López-Vázquez1, Lourdes Mozo1, Rebeca Alonso-Arias1, Beatriz Suárez-Álvarez1, José Ramón Vidal-Castiñeira1, Eduardo Arranz2, Umberto Volta3, Carlos Bousoño5, Marcos López-Hoyos67, Luís Rodrigo4 and Carlos López-Larrea17*

Author Affiliations

1 Department of Immunology, Hospital Universitario Central de Asturias, Oviedo 33006, Spain

2 Mucosal Immunology Laboratory, Department of Paediatrics and Immunology-IBGM, University of Valladolid, Valladolid, Spain

3 Department of Gastroenterology and Internal Medicine, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy

4 Department of Gastroenterology, Hospital Universitario Central de Asturias, Oviedo, Spain

5 Department of Paediatrics, Hospital Universitario Central de Asturias, Oviedo, Spain

6 Department of Immunology, Hospital Universitario Marqués de Valdecilla-IFIMAV, Santander, Spain

7 Fundación Renal “Iñigo Álvarez de Toledo”, Madrid, Spain

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BMC Medicine 2014, 12:34  doi:10.1186/1741-7015-12-34

Published: 25 February 2014



Overexpression of autologous proteins can lead to the formation of autoantibodies and autoimmune diseases. MHC class I polypeptide-related sequence A (MICA) is highly expressed in the enterocytes of patients with celiac disease, which arises in response to gluten. The aim of this study was to investigate anti-MICA antibody formation in patients with celiac disease and its association with other autoimmune processes.


We tested serum samples from 383 patients with celiac disease, obtained before they took up a gluten-free diet, 428 patients with diverse autoimmune diseases, and 200 controls for anti-MICA antibodies. All samples were also tested for anti-endomysium and anti-transglutaminase antibodies.


Antibodies against MICA were detected in samples from 41.7% of patients with celiac disease but in only 3.5% of those from controls (P <0.0001) and 8.2% from patients with autoimmune disease (P <0.0001). These antibodies disappeared after the instauration of a gluten-free diet. Anti-MICA antibodies were significantly prevalent in younger patients (P <0.01). Fifty-eight patients with celiac disease (15.1%) presented a concomitant autoimmune disease. Anti-MICA-positive patients had a higher risk of autoimmune disease than MICA antibody-negative patients (P <0.0001; odds ratio = 6.11). The risk was even higher when we also controlled for age (odds ratio = 11.69). Finally, we found that the associated risk of developing additional autoimmune diseases was 16 and 10 times as high in pediatric patients and adults with anti-MICA, respectively, as in those without.


The development of anti-MICA antibodies could be related to a gluten-containing diet, and seems to be involved in the development of autoimmune diseases in patients with celiac disease, especially younger ones.

Autoantibodies; Autoimmune diseases; Celiac disease; MICA; NKG2D; Type 1 diabetes mellitus